A numerical investigation on flow distribution and pressure drop characteristics in a plate-fin heat exchanger is presented. Influences from length and width of the distribution channel were particularly investigated. Flow distribution in the studied model was improved by increasing the length or reducing the width of the distribution channel, but at the cost of an increased pressure drop. The relationship of flow distribution and pressure drop was analyzed by the porous medium approach. A dynamic balance phenomenon was observed and further studied. Based on the results, a novel strategy for the attainment of flow uniformity, which causes negligible pressure drop variation, was proposed. Finally, a performance effectiveness factor was developed for predicting the effect of the proposed strategy on the performance of plate-fin heat exchangers.